PMID- 38070189
OWN - NLM
STAT- MEDLINE
DCOM- 20240205
LR  - 20240220
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 28
IP  - 1
DP  - 2024 Jan
TI  - Inhibition of ferroptosis by POLE2 in gastric cancer cells involves the 
      activation of NRF2/GPX4 pathway.
PG  - e17983
LID - 10.1111/jcmm.17983 [doi]
LID - e17983
AB  - Gastric cancer results in great cancer mortality worldwide, and inducing 
      ferroptosis dramatically improves the malignant phenotypes of gastric cancer. DNA 
      polymerase epsilon subunit 2 (POLE2) plays indispensable roles in tumorigenesis; 
      however, its involvement and molecular basis in ferroptosis and gastric cancer 
      are not clear. Human gastric cancer cells were infected with lentiviral vectors 
      to knock down or overexpress POLE2, and cell ferroptosis was detected. To further 
      validate the involvement of nuclear factor erythroid 2-related factor 2 (NRF2) 
      and glutathione peroxidase 4 (GPX4), lentiviral vectors were used. POLE2 
      expression was elevated in human gastric cancer cells and tissues and closely 
      correlated with clinicopathological features in gastric cancer patients. POLE2 
      knockdown was induced, while POLE2 overexpression inhibited ferroptosis of human 
      gastric cancer cells, thereby modulating the malignant phenotypes of gastric 
      cancer. Mechanistic studies revealed that POLE2 overexpression elevated NRF2 
      expression and activity and subsequently activated GPX4, which then prevented 
      lipid peroxidation and ferroptosis in human gastric cancer cells. In contrast, 
      either NRF2 or GPX4 silence significantly prevented POLE2 overexpression-mediated 
      inductions of cell proliferation, migration, invasion and inhibition of 
      ferroptosis. POLE2 overexpression inhibits ferroptosis in human gastric cancer 
      cells through activating NRF2/GPX4 pathway, and inhibiting POLE2 may be a crucial 
      strategy to treat gastric cancer.
CI  - (c) 2023 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Jian, Hui
AU  - Jian H
AUID- ORCID: 0009-0004-8714-5380
AD  - Department of Gastrointestinal Surgery, Affiliated Hospital of Jianghan 
      University, Wuhan, Hubei, China.
FAU - Chen, Zhi-Qiang
AU  - Chen ZQ
AD  - Department of Gastrointestinal Surgery, Affiliated Hospital of Jianghan 
      University, Wuhan, Hubei, China.
FAU - Du, Heng
AU  - Du H
AD  - Department of Gastrointestinal Surgery, Huanggang Central Hospital Affiliated to 
      Yangtze University, Huanggang, Hubei, China.
FAU - Liao, Ting
AU  - Liao T
AD  - Department of Gastroenterology, Affiliated Hospital of Jianghan University, 
      Wuhan, Hubei, China.
FAU - Sun, Yi-Chen
AU  - Sun YC
AD  - Department of Oncology, Affiliated Hospital of Jianghan University, Wuhan, Hubei, 
      China.
FAU - Ke, Dong
AU  - Ke D
AD  - Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, 
      Wuhan, Hubei, China.
FAU - Yu, Yang
AU  - Yu Y
AD  - Department of Gastrointestinal Surgery, Affiliated Hospital of Jianghan 
      University, Wuhan, Hubei, China.
LA  - eng
GR  - WJ2023M136/Scientific Research Project of Hubei Provincial Health Commission/
GR  - 2023KJZXB02/Scientific Research Foundation of Jianghan University/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231209
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (NF-E2-Related Factor 2)
RN  - EC 2.7.7.- (Nucleotidyltransferases)
RN  - 0 (Protein Subunits)
RN  - EC 2.7.7.7 (POLE2 protein, human)
SB  - IM
MH  - Humans
MH  - *Ferroptosis
MH  - Lentivirus
MH  - NF-E2-Related Factor 2
MH  - Nucleotidyltransferases
MH  - Protein Subunits
MH  - *Stomach Neoplasms
PMC - PMC10805511
OTO - NOTNLM
OT  - GPX4
OT  - POLE2
OT  - ferroptosis
OT  - gastric cancer
COIS- The authors declare no conflicts of interest.
EDAT- 2023/12/10 06:42
MHDA- 2024/01/25 06:43
PMCR- 2023/12/09
CRDT- 2023/12/09 16:12
PHST- 2023/09/14 00:00 [revised]
PHST- 2023/07/08 00:00 [received]
PHST- 2023/09/26 00:00 [accepted]
PHST- 2024/01/25 06:43 [medline]
PHST- 2023/12/10 06:42 [pubmed]
PHST- 2023/12/09 16:12 [entrez]
PHST- 2023/12/09 00:00 [pmc-release]
AID - JCMM17983 [pii]
AID - 10.1111/jcmm.17983 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2024 Jan;28(1):e17983. doi: 10.1111/jcmm.17983. Epub 2023 Dec 9.